The physiology and metabolism of ascorbic acid in the guinea pig is quite similar to that in man in many respects, e.g., tissue distribution and transport mechanisms, pool size, and urinary metabolites. These similarities coupled with considerations of small size, low cost, and ready availability suggest the suitability of the guinea pig as model system for the investigation of the basic physiology and metabolism of the vitamin in vivo. Preliminary experiments have documented the rapid catabolism of ascorbic acid by gut microflora in the guinea pig, raising the possibility that observed differences in excretory route and half-life between man and guinea pig are largely due to intestinal microflora. This hypothesis will be explored using previously established techniques of isotope excretion and ascorbic acid kinetic analysis in both conventional and germfree guinea pigs. Additional experiments will explore the physiological significance of the recently discovered biliary secretion of ascorbic acid in relation to its overall turnover. Comparison of ascorbic acid turnover in specific tissues and subcellular fractions will provide greater understanding of the physiological basis of the rapidly-and slowly-miscible ascorbate pools. An intriguing perturbation of the plasma ascorbate turnover curve, demonstrating a new facet of ascorbate metabolism in the guinea pig, will be further investigated in the proposed work. After initial characterization of the guinea pig model, the influence of dietary ascorbic acid intake and physiological stress upon ascorbic acid turnover and/or pool size (s) will be investigated.